They say a calorie is just a calorie, but a groundbreaking study from the University of Wisconsin School of Medicine and Public Health has turned that idea on its head. According to new research, reducing the intake of just one amino acid, isoleucine, can lead to a healthier and longer life, even if you consume more calories.
"We like to say a calorie is not just a calorie," says Dudley Lamming, the lead author of the study and a professor specializing in metabolism. He and his team found that cutting down on isoleucine, an essential amino acid found in many protein-rich foods, can extend the lifespan of mice, making them leaner and less frail as they age. This discovery was recently published in Cell Metabolism.
Amino acids are the building blocks of proteins, and it's well-known that their role goes beyond just calories. Interestingly, earlier data from the Survey of the Health of Wisconsin indicated that individuals with higher body mass indexes (BMI) typically consumed more isoleucine. This amino acid is abundant in eggs, dairy, soy protein, and numerous types of meat.
In their experiment, Lamming and his multi-disciplinary team provided mice with different diets: a balanced control diet, one reduced in several amino acids, and another specifically low in isoleucine. These mice were about six months old, comparable to a 30-year-old human, and could eat as much as they wanted.
"Very quickly, we saw the mice on the reduced isoleucine diet lose adiposity – their bodies got leaner, they lost fat," Lamming said. Meanwhile, mice on the low-amino-acid diet initially lost weight but then regained it, showing the specific impact of isoleucine reduction.
The results were quite astounding. Mice on a low-isoleucine diet lived longer – 33% longer for males and 7% longer for females. Their health metrics, from muscle strength and endurance to even tail use and hair loss, were significantly better compared to those on other diets.
While low-calorie diets and similar studies have been conducted on young mice before, starting this regimen in middle-aged mice and still seeing such benefits is particularly encouraging. It suggests dietary changes could have substantial impacts even if implemented later in life.
The study didn’t just assess lifespan. These mice were also healthier overall, maintaining steadier blood sugar levels and experiencing less age-related prostate enlargement. Moreover, males were less likely to develop tumors, a leading cause of death among the diverse strain of mice used in the study.
Interestingly, the mice on low-isoleucine diets consumed more calories, perhaps trying to compensate for their lower isoleucine intake. Yet, they burned more calories and maintained leaner body weights, changes driven primarily by metabolic alterations rather than increased physical activity.
The new insights also touch on the mTOR gene. This gene is noted for its role in aging across various species and is linked to a hormone thought to manage the body’s response to cold, considered for diabetes treatment in humans. However, the precise mechanisms through which low-isoleucine diets confer such health benefits remain a mystery.
Lamming believes that the gender differences in the study’s outcomes might offer crucial clues for future research. Males seemed to benefit more from the diet, hinting at underlying biological processes that we don't yet fully understand.
Human translation of this diet, however, is not straightforward. While people need isoleucine, and completely removing it from diets is no easy feat, the findings still hold promise. "We can’t just switch everyone to a low-isoleucine diet," Lamming acknowledges. "But narrowing these benefits down to a single amino acid gets us closer to understanding the biological processes and maybe potential interventions for humans, like an isoleucine-blocking drug."
Indeed, as data from the Survey of the Health of Wisconsin highlighted, there is a noticeable variation in isoleucine intake, with leaner individuals consuming less of it. Other lab data also suggest that overweight and obese individuals might be consuming more isoleucine than necessary.
Rozelyn Anderson, another UW-Madison professor involved in aging and metabolism research, points out the broader implications. “What Dudley’s team has uncovered is very interesting, and it speaks to the composition of proteins in the diet and how small differences can have quite large-scale effects,” she says. The challenge, as she sees it, is translating these findings to human diets that aren’t as controlled as a laboratory setting. The goal is to understand the underlying biology and make informed dietary recommendations.
Looking ahead, the research paves the way for future studies aiming to pinpoint how slight diet modifications can yield significant health benefits. The hope is that such understanding might eventually inform dietary guidelines or lead to pharmaceutical interventions that mimic these beneficial effects.
As researchers delve deeper into this intriguing connection between amino acid intake and health, it becomes clear that the mantra
